Perioperative Management of Anticoagulation in Patients with Atrial Fibrillation

Atrial fibrillation (AF) is one of the most common cardiac dysrhythmias and responsible for significant morbidity and mortality worldwide. In the United States, roughly 3 million patients suffer from AF and that number is likely to double by 2050.¹ One of the most concerning complications of AF is thrombosis—most notably stroke. AF-related stroke accounts for over 15% of all strokes and can result in significant disability, and even death. 

In an effort to reduce the risk of thrombotic events when warfarin (or another anticoagulant) is discontinued and/or reinitiated during the perioperative period, prescribers often use short-acting anticoagulants (eg, heparin or low-molecular weight heparin [LMWH]) to maintain therapeutic anticoagulation. While this practice is widely performed, it is largely based on theory and the safety and efficacy of such a strategy has recently been called into question.  
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A Case Study

RB is a 60-year-old black male who is taking warfarin 5 mg daily for a history of AF. In addition, RB has a history of hypertension and diabetes—both of which are well-controlled—and takes amlodipine 5 mg daily and metformin 1000 mg twice daily. As part of routine health maintenance, RB is scheduled to undergo a screening colonoscopy in 1 week. 

His international normalized ratio (INR) is 2.4 (goal 2-3). The gastroenterologist has requested RB stop his warfarin prior to the procedure in the event a polypectomy is required. 

Since RB’s warfarin therapy will be interrupted, will he need to start a LMWH in order to reduce his risk for blood clots?

Clinical Question

Traditionally, patients required to temporarily discontinue warfarin were bridged with enoxaparin (or other LMWH) as the heparinoid will mitigate the risks for a blood clot, but due to the short duration of action, still allow a nearly baseline level of anticoagulation during the surgical procedure. This strategy seems to maximize both the benefits in terms of reducing the risk of venous thromboembolism while minimizing the risk for bleeding during the surgical procedure. Do the benefits truly outweigh the risks?

Evidence 

The perceived severe consequences of thromboembolic events, combined with the low reported rate of bleeding with LMWHs (~1%), gives credibility to the strategy of using a LWMH during the warfarin interruption.² In patients with AF, the CHADS2 or CHA2DS2-VASc score is used to estimate the risk for thromboembolic events. These scoring systems can also potentially guide the decision on whether or not to bridge—higher scores confer higher risk, suggesting higher need for a LMWH. 

As no clear evidence existed to guide clinicians during these situations, reasonable clinical rationale was applied and many patients safely received bridge therapy during temporary warfarin interruptions. Despite this strategy having sound logic to support it, clinical evidence would be needed to confirm it.

The recently published BRIDGE (Effectiveness of Bridging Anticoagulation for Surgery) study evaluated such a strategy in patients with AF who are undergoing a surgical procedure requiring a warfarin dose interruption. Patients enrolled in the study had an average CHADS2 score of 2.3. Over 1800 patients were randomly assigned to either placebo or LMWH (dalteparin) during warfarin interruption. The primary outcome of arterial thromboembolism, which included stroke, systemic embolism, or transient ischemic attack, was low in both groups (no bridging: 0.4% vs bridging: 0.3%) and not statistically different. However, the risk of major and minor bleeding was significantly higher in the group receiving the LMWH (1.3% vs 3.2%; 12% vs 20.9%, respectively), thus demonstrating that the bleeding risks of bridge therapy clearly outweigh any potential benefit in reducing the risk for thromboembolic events.³ 

Clinical Application

The BRIDGE study clearly demonstrated that in moderate-risk patients with AF, employing a LMWH during warfarin interruption led to a higher rate of bleeding compared to placebo without reducing the risk for thromboembolic events. Given that the risks of bleeding outweigh the potential benefit, such a strategy should likely be avoided in low- or moderate-risk patients. 

However, in patient’s at high risk (CHADS2 score of 5 or 6), no evidence exists to guide this strategy.
As these patients carry a high risk for thromboembolic events, LMWH therapy may still be indicated, although this recommendation is based on clinical rationale alone. Given the disparate event rates in the BRIDGE study, it may be reasonable to conclude that even in high-risk patients, bridging with LMWHs may not be as beneficial as previously thought. Similar evidence has recently been published regarding bridge therapy in patients with a previous history of deep vein thrombosis or pulmonary embolism. 

As described by the BRIDGE trial, in moderate-risk patients using LMWH during a planned warfarin interruption led to a higher rate of bleeding compared to placebo without reducing the rate of thromboembolism.⁴ 

Outcome of the Case 

With a CHADS2 of 2, RB presented very similar to a patient followed in the BRIDGE study. Since he has only a moderate risk of thromboembolism, a strategy employing a LMWH during his planned warfarin interruption would likely lead to an unacceptably high rate of bleeding. Furthermore, the substantial cost associated with LMWH further widens the risk-to-benefit ratio, making such a strategy likely unwarranted in this setting. 

RB was counseled to discontinue his warfarin 4 days prior to his procedure and resume the warfarin at the discretion of the gastroenterologist, once hemostasis is achieved. His INR should be checked approximately 5 to 7 days after he resumes warfarin to ensure it has returned or is returning to the therapeutic range.

Eric A. Dietrich, PharmD, BCPS, graduated from UF College of Pharmacy in 2011 and completed a 2-year fellowship in family medicine where he was in charge of a coumadin clinic. He now works for the UF Colleges of Pharmacy and Medicine. 

Kyle Davis, PharmD, BCPS, graduated from the University of Florida College of Pharmacy in 2011 and completed a PGY-1 at Jackson Memorial Hospital and a PGY-2 in internal medicine at Indiana University Health and Butler College of Pharmacy. He currently works at Jackson Memorial Hospital in Miami, FL. 

References:

Kannel WB, Benjamin EJ. Status of the epidemiology of atrial fibrillation. Med Clin North Am. 2008;92(1):17-40, ix. 

Wells PS, Anderson DR, Rodger MA, et al. A randomized trial comparing 2 low-molecular-weight heparins for the outpatient treatment of deep vein thrombosis and pulmonary embolism. Arch Intern Med. 2005;165(7):733-738.

Douketis JD, Spyropoulos AC, Kaatz S, et al; BRIDGE Investigators. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med. 2015 Jun 22 [epub ahead of print]

Clark NP, Witt DM, Davies LE, et al. Bleeding, recurrent venous thromboembolism, and mortality risks during warfarin interruption for invasive procedures. JAMA Internal Med. 2015;175(7):1163-1168.